Non-invasive and minimally invasive denervation methods and systems for performing the same

ABSTRACT

A system and method can be used to denervate at least a portion of a bronchial tree. An energy emitter of an instrument is percutaneously delivered to a treatment site and outputs energy to damage nerve tissue of the bronchial tree. The denervation procedure can be performed without damaging non-targeted tissue. Minimally invasive methods can be used to open airways to improve lung function in subjects with COPD, asthma, or the like. Different sections of the bronchial tree can be denervated while leaving airways intact to reduce recovery times.

RELATED APPLICATIONS

This application is a continuation of application Ser. No. 15/596,192filed May 16, 2017, which in turn is a division of application Ser. No.14/541,931 filed Nov. 14, 2014, now U.S. Pat. No. 9,649,154 issued May16, 2017, which in turn is a continuation of application Ser. No.12/944,666 filed Nov. 11, 2010, now U.S. Pat. No. 8,911,439 issued Dec.16, 2014, which claims the benefit of U.S. Provisional Application No.61/260,350 filed Nov. 11, 2009, each of which is hereby fullyincorporated herein by reference.

BACKGROUND Technical Field

The present invention generally relates to non-invasive and minimallyinvasive denervation methods and systems and apparatuses for performingthose methods.

Description of the Related Art

Pulmonary diseases may cause a wide range of problems that adverselyaffect performance of the lungs. Pulmonary diseases, such as asthma andchronic obstructive pulmonary disease (“COPD”), may lead to increasedairflow resistance in the lungs. Mortality, health-related costs, andthe size of the population having adverse effects due to pulmonarydiseases are all substantial. These diseases often adversely affectquality of life. Symptoms are varied and often include cough,breathlessness, and wheeze. In COPD, for example, breathlessness may benoticed when performing somewhat strenuous activities, such as running,jogging, brisk walking, etc. As the disease progresses, breathlessnessmay be noticed when performing non-strenuous activities, such aswalking. Over time, symptoms of COPD may occur with less and less effortuntil they are present all of the time, thereby severely limiting aperson's ability to accomplish normal tasks.

Pulmonary diseases are often characterized by airway obstructionassociated with blockage of an airway lumen, thickening of an airwaywall, alteration of structures within or around the airway wall, orcombinations thereof. Airway obstruction can significantly decrease theamount of gas exchanged in the lungs resulting in breathlessness.Blockage of an airway lumen can be caused by excessive intraluminalmucus or edema fluid, or both. Thickening of the airway wall may beattributable to excessive contraction of the airway smooth muscle,airway smooth muscle hypertrophy, mucous glands hypertrophy,inflammation, edema, or combinations thereof. Alteration of structuresaround the airway, such as destruction of the lung tissue itself, canlead to a loss of radial traction on the airway wall and subsequentnarrowing of the airway.

Asthma can be characterized by contraction of airway smooth muscle,smooth muscle hypertrophy, excessive mucus production, mucous glandhypertrophy, and/or inflammation and swelling of airways. Theseabnormalities are the result of a complex interplay of localinflammatory cytokines (chemicals released locally by immune cellslocated in or near the airway wall), inhaled irritants (e.g., cold air,smoke, allergens, or other chemicals), systemic hormones (chemicals inthe blood such as the anti-inflammatory cortisol and the stimulantepinephrine), local nervous system input (nerve cells containedcompletely within the airway wall that can produce local reflexstimulation of smooth muscle cells and mucous glands and can contributeto inflammation and edema), and the central nervous system input(nervous system signals from the brain to smooth muscle cells, mucousglands and inflammatory cells carried through the vagus nerve). Theseconditions often cause widespread temporary tissue alterations andinitially reversible airflow obstruction that may ultimately lead topermanent tissue alteration and permanent airflow obstruction that makeit difficult for the asthma sufferer to breathe. Asthma can furtherinclude acute episodes or attacks of additional airway narrowing viacontraction of hyper-responsive airway smooth muscle that significantlyincreases airflow resistance. Asthma symptoms include recurrent episodesof breathlessness (e.g., shortness of breath or dyspnea), wheezing,chest tightness, and cough.

Emphysema is a type of COPD often characterized by the alteration oflung tissue surrounding or adjacent to the airways in the lungs.Emphysema can involve destruction of lung tissue (e.g., alveoli tissuesuch as the alveolar sacs) that leads to reduced gas exchange andreduced radial traction applied to the airway wall by the surroundinglung tissue. The destruction of alveoli tissue leaves areas ofemphysematous lung with overly large airspaces that are devoid ofalveolar walls and alveolar capillaries and are thereby ineffective atgas exchange. Air becomes “trapped” in these larger airspaces. This“trapped” air may cause over-inflation of the lung, and in the confinesof the chest restricts the in-flow of oxygen rich air and the properfunction of healthier tissue. This results in significant breathlessnessand may lead to low oxygen levels and high carbon dioxide levels in theblood. This type of lung tissue destruction occurs as part of the normalaging process, even in healthy individuals. Unfortunately, exposure tochemicals or other substances (e.g., tobacco smoke) may significantlyaccelerate the rate of tissue damage or destruction. Breathlessness maybe further increased by airway obstruction. The reduction of radialtraction may cause the airway walls to become “floppy” such that theairway walls partially or fully collapse during exhalation. Anindividual with emphysema may be unable to deliver air out of theirlungs due to this airway collapse and airway obstructions duringexhalation.

Chronic bronchitis is a type of COPD that can be characterized bycontraction of the airway smooth muscle, smooth muscle hypertrophy,excessive mucus production, mucous gland hypertrophy, and inflammationof airway walls. Like asthma, these abnormalities are the result of acomplex interplay of local inflammatory cytokines, inhaled irritants,systemic hormones, local nervous system, and the central nervous system.Unlike asthma where respiratory obstruction may be largely reversible,the airway obstruction in chronic bronchitis is primarily chronic andpermanent. It is often difficult for a chronic bronchitis sufferer tobreathe because of chronic symptoms of shortness of breath, wheezing,and chest tightness, as well as a mucus producing cough.

Different techniques can be used to assess the severity and progressionof pulmonary diseases. For example, pulmonary function tests, exercisecapacity, and quality of life questionnaires are often used to evaluatesubjects. Pulmonary function tests involve objective and reproduciblemeasures of basic physiologic lung parameters, such as total airflow,lung volume, and gas exchange. Indices of pulmonary function tests usedfor the assessment of obstructive pulmonary diseases include the forcedexpiratory volume in 1 second (FEV1), the forced vital capacity (FVC),the ratio of the FEV1 to FVC, the total lung capacity (TLC), airwayresistance and the testing of arterial blood gases. The FEV1 is thevolume of air a patient can exhale during the first second of a forcefulexhalation which starts with the lungs completely filled with air. TheFEV1 is also the average flow that occurs during the first second of aforceful exhalation. This parameter may be used to evaluate anddetermine the presence and impact of any airway obstruction. The FVC isthe total volume of air a patient can exhale during a forcefulexhalation that starts with the lungs completely filled with air. TheFEV1/FVC is the fraction of all the air that can be exhaled during aforceful exhalation during the first second. A FEV1/FVC ratio less than0.7 after the administration of at least one bronchodilator defines thepresence of COPD. The TLC is the total amount of air within the lungswhen the lungs are completely filled and may increase when air becomestrapped within the lungs of patients with obstructive lung disease.Airway resistance is defined as the pressure gradient between thealveoli and the mouth to the rate of air flow between the alveoli andthe mouth. Similarly, resistance of a given airway is defined as theratio of the pressure gradient across the given airway to the flow ofair through the airway. Arterial blood gases tests measure the amount ofoxygen and the amount of carbon dioxide in the blood and are the mostdirect method for assessing the ability of the lungs and respiratorysystem to bring oxygen from the air into the blood and to get carbondioxide from the blood out of the body.

Exercise capacity tests are objective and reproducible measures of apatient's ability to perform activities. A six minute walk test (6 MWT)is an exercise capacity test in which a patient walks as far as possibleover a flat surface in 6 minutes. Another exercise capacity testinvolves measuring the maximum exercise capacity of a patient. Forexample, a physician can measure the amount of power the patient canproduce while on a cycle ergometer. The patient can breathe 30 percentoxygen and the work load can increase by 5-10 watts every 3 minutes.

Quality of life questionnaires assess a patient's overall health andwell being. The St. George's Respiratory Questionnaire is a quality oflife questionnaire that includes 75 questions designed to measure theimpact of obstructive lung disease on overall health, daily life, andperceived well-being. The efficacy of a treatment for pulmonary diseasescan be evaluated using pulmonary function tests, exercise capacitytests, and/or questionnaires. A treatment program can be modified basedon the results from these tests and/or questionnaires.

Treatments, such as bronchial thermoplasty, involve destroying smoothmuscle tone by ablating the airway wall in a multitude of bronchialbranches within the lung thereby eliminating both smooth muscles andnerves in the airway walls of the lung. The treated airways are unableto respond favorably to inhaled irritants, systemic hormones, and bothlocal and central nervous system input. Unfortunately, this destructionof smooth muscle tone and nerves in the airway wall may thereforeadversely affect lung performance. For example, inhaled irritants, suchas smoke or other noxious substances, normally stimulate lung irritantreceptors to produce coughing and contracting of airway smooth muscle.Elimination of nerves in the airway walls removes both local nervefunction and central nervous input, thereby eliminating the lung'sability to expel noxious substances with a forceful cough. Eliminationof airway smooth muscle tone may eliminate the airway's ability toconstrict, thereby allowing deeper penetration of unwanted substances,such as noxious substances, into the lung.

Both asthma and COPD are serious diseases with growing numbers ofsufferers. Current management techniques, which include prescriptiondrugs, are neither completely successful nor free from side effects.Additionally, many patients do not comply with their drug prescriptiondosage regiment. Accordingly, it would be desirable to provide atreatment which improves resistance to airflow without the need forpatient compliance.

BRIEF SUMMARY

Some embodiments are directed to non-invasive or minimally invasivedenervation procedures. The denervation procedures can be performedwithout causing trauma that results in significant recovery periods.Non-invasive denervation methods can involve delivering energy fromenergy sources positioned external to the subject. The energy is aimedat targeted tissue to minimize, limit, or substantially eliminateappreciable damage to non-targeted tissue. Minimally invasivedenervation procedures can involve percutaneously delivering aninstrument.

Denervation of hollow organs, such as the lung bronchus, can be due tothe creation of lesions with radiofrequency ablation that are of asufficient depth when generated on the outside of the organ to penetratethe adventitial tissue layers where nerve trunks are anatomicallylocated. In the example of lung denervation, ablating nerve trunks alongthe outside of both the right and left main bronchi effectivelydisconnects airway smooth muscle which lines the inside of the lungairways and mucus producing glands located with the airways from thevagus nerve. When this occurs, airway smooth muscle relaxes and mucusproduction is decreased. Nervous system mediated inflammation and edemawill decrease as well. These changes reduce airway obstruction forsubjects with COPD, asthma, or the like. Reduced airway obstructionmakes breathing easier which improves the subject's quality of life andhealth status. Tests and questionnaires can be used to evaluate andmonitor the subject's health.

Some embodiments are directed to a percutaneously deliverable apparatuscapable of performing a denervation procedure. The apparatus can ablatetargeted nerve tissue to denervate at least a portion of a lung. Aminimally invasive access device can be used to percutaneously deliverthe apparatus and can be a needle, a trocar, a robotic catheter, amediastinoscope, a port, or a thoracoscope. Direct or remotevisualization techniques (e.g., ultrasound guidance, endoscopy,radiologic guidance, etc.) can be used to position the apparatus.

The apparatus can be an instrument insertable directly into a holloworgan (e.g., through the mouth and into the esophagus or stomach) orinserted through the instrument channel of an endoscope (e.g.,gastroscope, esophagoscope, or the like). The instrument has a flexibleelongate shaft that carries one or more ablation elements. The ablationelements can be energy emitters, such as electrodes. The apparatus canbe delivered through an opening in the subject's chest. The instrumentcan be brought into direct contact with the outer surface of thebronchial tree or lung while extending through the hollow organ.

The apparatus can be an instrument insertable directly into a largeperipheral artery (e.g., femoral artery, brachial artery, or the like)and advanced through the arterial tree, into the aorta, and then intoone or more bronchial arteries traveling along the main stem bronchi.The instrument has a flexible elongate shaft that carries one or moreablation elements. The ablation elements can be energy emitters, such aselectrodes. The bronchial arteries are often located in close proximityto the vagus nerve trunks traveling along the outside of the bronchialtree. Placement of the instrument in one or more bronchial arteriesbrings the instrument with its ablation elements into close proximity tothe vagus nerve trunks traveling along the outside of the bronchialtree. Advancement of the instrument and placement in the bronchialarteries can be guided by a variety of imaging modalities (e.g.,fluoroscopy, ultrasound, CT scans, or the like).

In some embodiments, an instrument has an activatable section capable ofintimately contacting a surface of an airway (either an outer surface oran inner surface). The activatable section can include one or moreselectively activatable energy emitters, ablation elements, or the like.The activatable section can preferentially treat the posterior portionof the main lung airways or other targeted region(s) of airways.

A system for treating a subject includes an extraluminal elongateassembly dimensioned to move around the outside of the airway of abronchial tree and an access device. The elongate assembly is adapted toattenuate signals transmitted by nerve tissue, such as nerve tissue ofnerve trunks, while not irreversibly damaging adjacent anatomicalstructures. The elongate assembly can include at least one ablationelement, which includes one or more electrodes operable to outputradiofrequency energy.

Some methods involve minimally invasive denervation of at least aportion of a lung. The method comprises damaging nerve tissue of a firstmain bronchus to substantially prevent nervous system signals fromtraveling to most or substantially all distal bronchial branchesconnected to the first main bronchus. The nerve tissue, in certainembodiments, is positioned between a trachea and a lung through whichthe bronchial branches extend. The airway can remain intact while thenerve tissue is damaged.

The method, in some embodiments, further includes damaging nerve tissueof a second main bronchus to substantially prevent nervous systemsignals from traveling to most or substantially all distal bronchialbranches connected to the second main bronchus. An apparatus used todamage the nerve tissue can be percutaneously delivered with theassistance of sonographic guidance, radiologic guidance, roboticguidance, mediastinoscopic guidance, thoracoscopic guidance, or otherminimally invasive surgery visualization techniques.

In some embodiments, a method for treating a subject includes moving atip of an instrument through at least a portion of a subject's skin toposition the instrument next to nerve tissue. A desired amount of nervetissue can then be damaged using the instrument. Some methods includedamaging nerve tissue along a right main bronchus and ablating nervetissue along the left main bronchus to denervate a significant portionof the bronchial tree. In other embodiments, denervating a portion ofthe bronchial tree comprises destroying at least one nerve trunk at aposition that is within at least one of the left and right lung. Thedenervation process, in some embodiments, is performed withoutpermanently damaging other tissue structures. In some denervationprocedures, substantially all of the nerve trunks extending along atubular section of an airway are damaged to prevent substantially allnervous system signals transmitted along the airway from traveling pastthe denervated portion without destroying the airway.

In yet other embodiments, a method for denervating a bronchial tree of asubject includes moving an energy emitter of an instrument through thesubject's skin. The energy emitter is positioned proximate to an airway.Nerve tissue of the bronchial tree is damaged using the energy emitterwhile the energy emitter is positioned outside of the airway. The energyemitter can output a sufficient amount of at least one of radiofrequencyenergy, microwave energy, radiation energy, high intensity focusedultrasound energy (HIFU), thermal energy, or combinations thereof todamage the nerve tissue. In radiofrequency ablation, the instrument maycool and protect nontargeted tissue. High intensity focused ultrasoundenergy can be delivered to specific targeted tissue to mitigate damageof nontargeted tissue. The instrument is removed from the subject,leaving the airway intact.

Non-invasive denervation methods can be used to denervate a subject'slungs. An external energy source can deliver energy to targeted tissueto form lesions. The lesions can be formed at a depth of 1 mm to 2 mmalong an airway to insure that a nerve trunk is destroyed withoutdestroying the entire airway wall.

A method in some embodiments comprises moving a distal section of aninstrument through a subject's skin. Most of a bronchial tree isdenervated using the instrument to substantially prevent nervous systemsignals from traveling to substantially all branches of the bronchialtree. The distal section can be percutaneously delivered to minimizetrauma and reduce recovery time. The method can be performed withoutsevering airways, removing airways, or otherwise damaging the entirecircumference of the denervated airway. In some embodiments, the entireprocedure is performed without severing the entire airway. The airwaycan continue to function after the procedure.

A denervation method includes moving an energy emitter of an instrumentthrough the subject's skin. Nerve tissue is altered (e.g., damaged,ablated, etc.) using energy from the energy emitter while the energyemitter is positioned outside of an airway or organ. The instrument isremoved from the subject without destroying the airway or organ. Incertain embodiments, the airway remains intact through the entiredenervation process such that the airway maintains the health of distalportions of the lung. The denervation method can be used to denervateone or both lungs.

In some embodiments, a distal section of an instrument is wrapped aroundan airway to position at least one energy emitter with respect to nervetissue. The energy emitter can output energy to damage the nerve tissue.Visualization can be used to view the airway. In certain embodiments,the outside of the airway is visualized while performing an ablationprocedure or positioning the energy emitter. Visualization can beachieved using at least one of a thoracoscope, an ultrasonic device, anda fluoroscopy system.

A wide range of different types of body structures can be treated usingenergy. Non-limiting exemplary body structures include airways, thetrachea, esophagus, vessels (e.g., blood vessels), the urethra, or othertargeted structures. In certain embodiments, an instrument isendovascularly positioned in a blood vessel to position a distal portionof the instrument proximate to an airway nerve or other target region.Energy is delivered from the instrument to damage the airway nerve suchthat nerve signals to the airway are attenuated.

In some embodiments, a method for denervating a bronchial tree or otherbody structure of a subject includes moving an energy emitter of aninstrument through the subject's skin. Nerve tissue is damaged usingenergy from the energy emitter while the energy emitter is positionedoutside of the airway or body structure. In certain procedures, theinstrument is removed from the subject without severing the entireairway. The procedure can be performed without puncturing the wall ofthe airway or body structure.

In yet other embodiments, a method for treating a subject comprisesdelivering emitting energy from an external energy source positionedoutside of the subject's body through the subject's skin towardstargeted nerve tissue of a bronchial tree. The nerve tissue is damagedusing the energy while the external energy source is outside thesubject's body. The external energy source can be placed against orspaced apart from the subject's skin.

In further embodiments, a method comprises percutaneously delivering adistal section of an instrument through a subject's skin such that thedistal section is positioned to damage nerve tissue of a bronchial tree,blood vessel, or other body structure. In bronchial tree procedures, atleast a portion of a bronchial tree in a subject's lung is denervatedusing the instrument to substantially prevent nervous system signalsfrom traveling to a portion of the bronchial tree. In vascularprocedures, a catheter is endovascularly positioned a in a blood vesselto position a distal portion of the catheter proximate to an airwaynerve. The catheter is used to ablate nerve tissue.

In certain embodiments, an instrument is endovascularly positioned in ablood vessel (e.g., a bronchial artery or other vessel) to position adistal portion of the instrument proximate to an airway structure, suchas a nerve. Energy is delivered from the instrument to damage the airwaynerve such that nerve signals to the airway are attenuated. Othertissues can also be targeted.

One or more electrodes carried by the distal portion of the catheter canoutput radiofrequency energy or ultrasound energy. The electrode can becoupled to an outside surface of the distal portion or positioned withinthe distal portion. By delivering the energy, nerve signals can beattenuated so as to reduce constriction of the airway. In someembodiments, the constriction is permanently eliminated. In yet otherprocedures, nerve signals are attenuated so as to inhibit constrictionof smooth muscle in the airway.

In other procedures, an instrument is passed through a subject's mouthand into the esophagus. The distal section of the instrument can bemanipulated to position the distal section of the instrument proximateto the bronchial tree. In certain embodiments, the distal section canpush against the wall of the esophagus to position an ablation assemblyproximate to the left main bronchus or the right main bronchus. Withoutpuncturing the esophagus wall, the ablation assembly can deliver energyto the nerve tissue with or without employing differential cooling. Theablation assembly can remain within the lumen of the esophagusthroughout the ablation process.

The instruments can be passed through openings in the esophagus, thetrachea, the left main bronchus and/or the right main bronchus. To passan instrument out of the trachea, an opening can be formed in the wallof the trachea. The instrument can be moved through the opening andproximate to nerve tissue of an airway. The nerve tissue can be ablatedwhile the instrument extends through the trachea wall and alongside theairway. In other procedures, a puncture can be formed along the leftand/or right main bronchus. The instrument can be delivered through theopening and can wrap around the bronchus to destroy or ablate tissue.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

In the Figures, identical reference numbers identify similar elements oracts.

FIG. 1 is an illustration of lungs, blood vessels, and nerves near toand in the lungs.

FIG. 2 is an illustration of a system positioned to treat a left mainbronchus.

FIG. 3 is a cross-sectional view of an airway of a bronchial tree takenalong a line 3-3 of FIG. 2.

FIG. 4 is a cross-sectional view of a constricted airway and mucus is inan airway lumen and an instrument positioned next to the airway.

FIG. 5 is a cross-sectional view of an airway with an intraluminalinstrument inside an airway and an instrument positioned outside theairway.

FIGS. 6-9 are side elevational views of distal sections of instruments.

FIG. 10 is an illustration of an instrument surrounding a left mainbronchus.

FIG. 11 is a cross-sectional view of the left main bronchus of takenalong a line 11-11 of FIG. 10.

FIG. 12 is an illustration of an external treatment system and asubject.

DETAILED DESCRIPTION

FIG. 1 illustrates human lungs 10 having a left lung 11 and a right lung12. A trachea 20 extends downwardly from the nose and mouth and dividesinto a left main bronchus 21 and a right main bronchus 22. The left mainbronchus 21 and right main bronchus 22 each branch to form lobar,segmental bronchi, and sub-segmental bronchi, which have successivelysmaller diameters and shorter lengths in the outward direction (i.e.,the distal direction). A main pulmonary artery 30 originates at a rightventricle of the heart and passes in front of a lung root 24. At thelung root 24, the artery 30 branches into a left and right pulmonaryartery, which in turn branch to form a network of branching bloodvessels. These blood vessels can extend alongside airways of a bronchialtree 27. The bronchial tree 27 includes the left main bronchus 21, theright main bronchus 22, bronchioles, and alveoli. Vagus nerves 41, 42extend alongside the trachea 20 and branch to form nerve trunks 45.

The left and right vagus nerves 41, 42 originate in the brainstem, passthrough the neck, and descend through the chest on either side of thetrachea 20. The vagus nerves 41, 42 spread out into nerve trunks 45 thatinclude the anterior and posterior pulmonary plexuses that wrap aroundthe trachea 20, the left main bronchus 21, and the right main bronchus22. The nerve trunks 45 also extend along and outside of the branchingairways of the bronchial tree 27. Nerve trunks 45 are the main stem of anerve, comprising a bundle of nerve fibers bound together by a toughsheath of connective tissue.

The primary function of the lungs 10 is to exchange oxygen from air intothe blood and to exchange carbon dioxide from the blood to the air. Theprocess of gas exchange begins when oxygen rich air is pulled into thelungs 10. Contraction of the diaphragm and intercostal chest wallmuscles cooperate to decrease the pressure within the chest to cause theoxygen rich air to flow through the airways of the lungs 10. Forexample, air passes through the mouth and nose, the trachea 20, thenthrough the bronchial tree 27. The air is ultimately delivered to thealveolar air sacs for the gas exchange process.

Oxygen poor blood is pumped from the right side of the heart through thepulmonary artery 30 and is ultimately delivered to alveolar capillaries.This oxygen poor blood is rich in carbon dioxide waste. Thinsemi-permeable membranes separate the oxygen poor blood in capillariesfrom the oxygen rich air in the alveoli. These capillaries wrap aroundand extend between the alveoli. Oxygen from the air diffuses through themembranes into the blood, and carbon dioxide from the blood diffusesthrough the membranes to the air in the alveoli. The newly oxygenenriched blood then flows from the alveolar capillaries through thebranching blood vessels of the pulmonary venous system to the heart. Theheart pumps the oxygen rich blood throughout the body. The oxygen spentair in the lung is exhaled when the diaphragm and intercostal musclesrelax and the lungs and chest wall elastically return to the normalrelaxed states. In this manner, air can flow through the branchingbronchioles, the bronchi 21, 22, and the trachea 20 and is ultimatelyexpelled through the mouth and nose.

A network of nerve tissue of the autonomic nervous system senses andregulates activity of the respiratory system and the vasculature system.Nerve tissue includes fibers that use chemical and electrical signals totransmit sensory and motor information from one body part to another.For example, the nerve tissue can transmit motor information in the formof nervous system input, such as a signal that causes contraction ofmuscles or other responses. The fibers can be made up of neurons. Thenerve tissue can be surrounded by connective tissue, i.e., epineurium.The autonomic nervous system includes a sympathetic system and aparasympathetic system. The sympathetic nervous system is largelyinvolved in “excitatory” functions during periods of stress. Theparasympathetic nervous system is largely involved in “vegetative”functions during periods of energy conservation. The sympathetic andparasympathetic nervous systems are simultaneously active and generallyhave reciprocal effects on organ systems. While innervation of the bloodvessels originates from both systems, innervation of the airways islargely parasympathetic in nature and travels between the lung and thebrain in the right vagus nerve 42 and the left vagus nerve 41.

FIG. 2 shows a minimally invasive system 200 capable of treating therespiratory system to enhance lung function. The subject may suffer fromCOPD, asthma, or the like and, thus, the lungs 10 may perform poorly. Todecrease air flow resistance to increase gas exchange, the system 200can be used to perform a denervation procedure. A distal section 214 ofan instrument 204 can affect nerve tissue, which can be part of a nervetrunk inside or outside of the lungs. The nerve tissue can be ablated topermanently dilate the airways and/or decrease airway mucus productionor airway inflammation and edema.

The instrument 204 can be used to attenuate the transmission of signalstraveling along the vagus nerves 41, 42 that cause or mediate musclecontractions, mucus 150 production, inflammation, edema, and the like.Attenuation can include, without limitation, hindering, limiting,blocking, and/or interrupting the transmission of signals. For example,the attenuation can include decreasing signal amplitude of nerve signalsor weakening the transmission of nerve signals. Decreasing or stoppingnervous system input to distal airways can alter airway smooth muscletone, airway mucus production, airway inflammation, and the like,thereby controlling airflow into and out of the lungs 10. Decreasing orstopping sensory input from the airways and lungs to local effectorcells or to the central nervous system can also decrease reflexbronchoconstriction, reflex mucous production, release of inflammatorymediators, and nervous system input to other cells in the lungs ororgans in the body that may cause airway wall edema. In someembodiments, the nervous system input can be decreased tocorrespondingly decrease airway smooth muscle tone. In some embodiments,the airway mucus production can be decreased a sufficient amount tocause a substantial decrease in coughing and/or in airflow resistance.In some embodiments, the airway inflammation can be decreased asufficient amount to cause a substantial decrease in airflow resistanceand ongoing inflammatory injury to the airway wall. Signal attenuationmay allow the smooth muscles to relax, prevent, limit, or substantiallyeliminate mucus production by mucous producing cells, and decreaseinflammation. In this manner, healthy and/or diseased airways can bealtered to adjust lung function. After treatment, various types ofquestionnaires or tests can be used to assess the subject's response tothe treatment. If needed or desired, additional procedures can beperformed to reduce the frequency of coughing, decrease breathlessness,decrease wheezing, and the like.

Main bronchi 21, 22 (i.e., airway generation 1) of FIGS. 1 and 2 can betreated to affect distal portions of the bronchial tree 27. In someembodiments, the left and right main bronchi 21, 22 are treated atlocations along the left and right lung roots 24 and outside of the leftand right lungs 11, 12. Treatment sites can be distal to where vagusnerve branches connect to the trachea and the main bronchi 21, 22 andproximal to the lungs 11, 12. A single treatment session involving twotherapy applications can be used to treat most of or the entirebronchial tree 27. Substantially all of the bronchial branches extendinginto the lungs 11, 12 may be affected to provide a high level oftherapeutic effectiveness. Because the bronchial arteries in the mainbronchi 21, 22 have relatively large diameters and high heat sinkingcapacities, the bronchial arteries may be protected from unintendeddamage due to the treatment.

Nerve tissue distal to the main bronchi can also be treated, such asnerve tissue positioned outside the lung which run along the right orleft main bronchi, the lobar bronchii, and bronchus intermedius. Theintermediate bronchus is formed by a portion of the right main bronchusand includes origin of the middle and lower lobar bronchii. The distalsection 214 can be positioned alongside higher generation airways (e.g.,airway generations >2) to affect remote distal portions of the bronchialtree 27. Different procedures can be performed to denervate a portion ofa lobe, an entire lobe, multiple lobes, or one lung or both lungs. Insome embodiments, the lobar bronchi are treated to denervate lung lobes.For example, one or more treatment sites along a lobar bronchus may betargeted to denervate an entire lobe connected to that lobar bronchus.Left lobar bronchi can be treated to affect the left superior lobeand/or the left inferior lobe. Right lobar bronchi can be treated toaffect the right superior lobe, the right middle lobe, and/or the rightinferior lobe. Lobes can be treated concurrently or sequentially. Insome embodiments, a physician can treat one lobe. Based on theeffectiveness of the treatment, the physician can concurrently orsequentially treat additional lobe(s). In this manner, differentisolated regions of the bronchial tree can be treated.

Each segmental bronchus may be treated by delivering energy to a singletreatment site along each segmental bronchus. Nerve tissue of eachsegmental bronchus of the right lung can be destroyed. In someprocedures, one to ten applications of energy can treat most of orsubstantially all of the right lung. Depending on the anatomicalstructure of the bronchial tree, segmental bronchi can often bedenervated using one or two applications of energy.

Function of other tissue or anatomical features, such as the mucousglands, cilia, smooth muscle, body vessels (e.g., blood vessels), andthe like can be maintained when nerve tissue is ablated. Nerve tissueincludes nerve cells, nerve fibers, dendrites, and supporting tissue,such as neuroglia. Nerve cells transmit electrical impulses, and nervefibers are prolonged axons that conduct the impulses. The electricalimpulses are converted to chemical signals to communicate with effectorcells or other nerve cells. By way of example, a portion of an airway ofthe bronchial tree 27 can be denervated to attenuate one or more nervoussystem signals transmitted by nerve tissue. Denervating can includedamaging all of the nerve tissue of a section of a nerve trunk along anairway to stop substantially all the signals from traveling through thedamaged section of the nerve trunk to more distal locations along thebronchial tree or from the bronchial tree more proximally to the centralnervous system. Additionally, signals that travel along nerve fibersthat go directly from sensory receptors (e.g., cough and irritantreceptors) in the airway to nearby effector cells (e.g., postganglionicnerve cells, smooth muscle cells, mucous cells, inflammatory cells, andvascular cells) will also be stopped. If a plurality of nerve trunksextends along the airway, each nerve trunk can be damaged. As such, thenerve supply along a section of the bronchial tree can be cut off. Whenthe signals are cut off, the distal airway smooth muscle can relaxleading to airway dilation, mucous cells decrease mucous production, orinflammatory cells stop producing airway wall swelling and edema. Thesechanges reduce airflow resistance so as to increase gas exchange in thelungs 10, thereby reducing, limiting, or substantially eliminating oneor more symptoms, such as breathlessness, wheezing, chest tightness, andthe like. Tissue surrounding or adjacent to the targeted nerve tissuemay be affected but not permanently damaged. In some embodiments, forexample, the bronchial blood vessels along the treated airway candeliver a similar amount of blood to bronchial wall tissues and thepulmonary blood vessels along the treated airway can deliver a similaramount of blood to the alveolar sacs at the distal regions of thebronchial tree 27 before and after treatment. These blood vessels cancontinue to transport blood to maintain sufficient gas exchange. In someembodiments, airway smooth muscle is not damaged to a significantextent. For example, a relatively small section of smooth muscle in anairway wall which does not appreciably impact respiratory function maybe reversibly altered. If energy is used to destroy the nerve tissueoutside of the airways, a therapeutically effective amount of energydoes not reach a significant portion of the non-targeted smooth muscletissue.

Any number of procedures can be performed on one or more of these nervetrunks to affect the portion of the lung associated with those nervetrunks. Because some of the nerve tissue in the network of nerve trunkscoalesces into other nerves (e.g., nerves connected to the esophagus,nerves though the chest and into the abdomen, and the like), specificsites can be treated to minimize, limit, or substantially eliminateunwanted damage of other nerves. Some fibers of anterior and posteriorpulmonary plexuses coalesce into small nerve trunks which extend alongthe outer surfaces of the trachea 20 and the branching bronchi andbronchioles as they travel outward into the lungs 10. Along thebranching bronchi, these small nerve trunks continually ramify with eachother and send fibers into the walls of the airways.

Referring to FIGS. 2 and 3, the distal section 214 is positioned withinthe chest outside of the airway 100. An activatable element in the formof an energy emitter 209 (illustrated in dashed line) is configured todamage nerve tissue 45, illustrated as a vagus nerve branch. Vagus nervetissue includes efferent fibers and afferent fibers oriented parallel toone another within a nerve branch. The efferent nerve tissue transmitssignals from the brain to airway effector cells, mostly airway smoothmuscle cells and mucus producing cells. The afferent nerve tissuetransmits signals from airway sensory receptors, which respond toirritants, and stretch to the brain. There is a constant, baseline tonicactivity of the efferent vagus nerve tissues to the airways which causesa baseline level of smooth muscle contraction and mucous secretion.

The energy emitter 209 can ablate the efferent and/or the afferenttissues to control airway smooth muscle (e.g., innervate smooth muscle),mucous secretion, nervous mediated inflammation, and tissue fluidcontent (e.g., edema). The contraction of airway smooth muscle, excessmucous secretion, inflammation, and airway wall edema associated withpulmonary diseases often results in relatively high air flow resistancecausing reduced gas exchange and decreased lung performance.

The instrument 204 can be delivered through a percutaneous opening inthe chest, back, or other suitable location. Potential access locationsinclude between the ribs in the chest, between the ribs in apara-sternal location, between the ribs along the back or side of thesubject, from a subxiphoid location in the chest, or through thepre-sternal notch superior to the manubrium. As used herein, the term“percutaneous” and derivations thereof refer generally to medicalprocedures that involve accessing internal organs via an opening, suchas a puncture or small incision in a subject's skin and may involve theuse of an access apparatus, such as the access apparatus 210. The accessapparatus 210 can be in the form of a trocar, a cannula, a port, asleeve, or other less-invasive access device, along with an endoscope, athoracoscope, or other visualization device. The distal section 214 canbe relatively sharp to puncture and pass through tissue. A stylet can bepositioned in a lumen in the instrument 204 and can have a relativelysharp tip to directly puncture the skin. After the stylet is insertedinto the skin, the instrument 204 can be moved along the stylet throughthe user's skin into and between internal organs.

The instrument 204 may be visualized using fluoroscopy, computedtomography (CT), thoracoscopy, ultrasound, or other imaging modalities,and may have one or more markers (e.g., radiopaque marks), or dyes(e.g., radiopaque dyes), or other visual features. The visual featurescan help increase the instrument's visibility, including theinstrument's radiopacity or ultrasonic visibility.

An instrument shaft 207 of FIG. 2 can be made of a generally flexiblematerial to allow delivery along tortuous paths to remote and deepsites. The distal section 214 can be steered or otherwise manipulatedusing a steering assembly 208. The distal section 214 can be deflectedlaterally or shaped into a desired configuration to allow enhancednavigation around thoracic structures. To deliver energy to a treatmentsite, the distal section 214 can assume a treatment configuration. Thetreatment configuration can be a serpentine configuration, a helicalconfiguration, a spiral configuration, a straight configuration, or thelike. U.S. patent application Ser. No. 12/463,304, filed on May 8, 2009,and U.S. patent application Ser. No. 12/913,702, filed on Oct. 27, 2010,describe catheters and apparatuses that can assume these types ofconfigurations and can be used to perform the methods disclosed herein.Each of these applications is incorporated by reference in its entirety.Conventional electrode catheters or ablation catheters can also be usedto perform at least some methods disclosed herein.

To damage nerve tissue 45, the distal section 214 can be at differentorientations, including transverse to the nerve trunk 45, generallyparallel to the nerve trunk 45, or any other suitable orientation withrespect to the airway 100. If the tissue is ablated using chemicals, thedistal section 214 can puncture the nerve trunk 45 and deliver the agentdirectly to nerve tissue.

As used herein, the term “energy” is broadly construed to include,without limitation, thermal energy, cryogenic energy (e.g., coolingenergy), electrical energy, acoustic energy (e.g., ultrasonic energy),microwave energy, radiofrequency energy, high voltage energy, mechanicalenergy, ionizing radiation, optical energy (e.g., light energy), andcombinations thereof, as well as other types of energy suitable fortreating tissue. The energy emitter 209 of FIG. 3 can include one ormore electrodes (e.g., needle electrodes, bipolar electrodes, ormonopolar electrodes) for outputting energy, such as ultrasound energy,radiofrequency (RF) energy, radiation, or the like. The electrodes canoutput a sufficient amount of RF energy to form a lesion at theperiphery of the airway 100. To avoid damaging smooth muscle tissue, alesion 219 (shown in phantom line in FIG. 3) can have a depth less thanor equal to about 2 mm. In some embodiments, the lesion depth D can beless than about 1 mm to localize tissue damage. Thermal energy emitters209 can be resistive heaters or thermally conducting elements. To treattissue with microwave energy, the energy emitter 209 can include one ormore microwave antennas. In optical embodiments, the energy emitter 209includes one or more lenses or reflector(s) capable of outputting lightdelivered via one or more optical fibers. An external light source(e.g., a lamp, an array of light emitting diodes, or the like) canoutput light that is delivered through the shaft 207 to the energyemitter 209. In other embodiments, the energy emitter 209 is a lightsource, such as a light-emitting diode (LED) or laser diode.Photodynamic agents or light activatable agents can be used to ablatetissue. In yet other embodiments, the energy emitter 209 can include adispenser (e.g., a nozzle, an orifice, etc.) for delivering a substance(e.g., a chemical agent, a high temperature fluid, a cutting jet, etc.)that kills or damages targeted tissue. Multiple emitters can be usedsequentially or simultaneously to treat tissue. For example, an energyemitter in the form of a dispenser can mechanically damage surfacetissue while another energy emitter outputs radiofrequency or microwaveenergy to destroy deep tissue.

For mechanical denervation, the distal section 214 can mechanicallydamage tissue by cutting, abrading, or tearing nerve tissue. A minimalamount of tissue adjacent to the nerve tissue 45 may also be damaged.The damaged non-targeted tissue can heal without any appreciabledecrease in lung function. In embodiments, the distal section 214comprises a morcellation device.

The distal section 214 can comprise one or more energy absorptiondevices for absorbing energy from a remote energy source. The remoteenergy source can be a microwave energy source, a radiofrequency energysource, an ultrasound energy source, or a radiation energy source andcan be positioned outside the subject's body or located in another bodystructure, such as the esophagus, airway (trachea or bronchus), orelsewhere in the subject's body. The distal section 214 can be heated bythe remote energy source to a sufficient temperature to damage targetedtissue. Additionally or alternatively, the element 209 can include areflector to reflect energy from a remote energy source. The reflectedenergy can create a pattern (e.g., interference pattern) to control theamplitude of energy waves at the target site.

With continued reference to FIG. 2, the controller 221 can include oneor more processors, microprocessors, digital signal processors (DSPs),field programmable gate arrays (FPGA), and/or application-specificintegrated circuits (ASICs), memory devices, buses, power sources, andthe like. For example, the controller 221 can include a processor incommunication with one or more memory devices. Buses can link aninternal or external power supply to the processor. The memories maytake a variety of forms, including, for example, one or more buffers,registers, random access memories (RAMs), and/or read only memories(ROMs). The controller 221 may also include a display, such as a screen,and can be a closed loop system, whereby the power to the distal section214 is controlled based upon feedback signals from one or more sensors212 (see FIG. 3) configured to transmit (or send) one or more signalsindicative of one or more tissue characteristics, energy distribution,tissue temperature, or any other measurable parameters of interest.Based on those readings, the controller 221 can then adjust operation ofthe distal section 214. By way of example, the controller 221 cancontrol the amount of energy delivered from the energy source 217 (e.g.,one or more batteries or other energy storage devices) to the energyemitter 209. The sensor 212 can be a temperature sensor. If thetemperature of the peripheral tissue of the airway 100 becomes too hot,the distal section 214 can cool the tissue using one or more Peltierdevices, cooling balloons, or other types of cooling features. Currentsensors or voltage sensors 212 can be used to measure the tissueimpedance. Alternatively, the controller 221 can be an open loop systemwherein the operation is set by user input. For example, the system 200may be set to a fixed power mode. It is contemplated that the system 200can be repeatedly switched between a closed loop mode and an open loopmode to treat different types of sites.

The instrument 204 can also include any number of different types ofvisualization devices, such as cameras, optical fibers, lenses, ormirrors. Ultrasound or other types of energy-based viewing systems canbe used to visualize deep targeted tissues. Surface tissues can betargeted using direct visualization while deeper tissues aresubsequently targeted using ultrasound.

FIG. 4 shows a constricted, edematous and mucous filled airway 100 thatcan be dilated and can have mucous production and edema decreased byablating the nerve tissue 45. As used herein, the term “ablate,”including variations thereof, refers, without limitation, to destroyingor permanently damaging, injuring, or traumatizing tissue. For example,ablation may include localized tissue destruction, cell lysis, cell sizereduction, necrosis, or combinations thereof. In the context ofpulmonary ablation applications, the term “ablation” includessufficiently altering nerve tissue properties to substantially blocktransmission of electrical signals through the ablated nerve tissue.Ablating all of the nerve trunks along the airway prevents nerve signalsfrom traveling distally along the airway 100 and causes the smoothmuscle 114 to relax to open the airway 100.

In RF ablation, RF energy causes heating of the nerve tissue 45 and,ultimately, the formation of the lesion 219. The nerve tissue isdestroyed without removing a significant amount of airway tissue, ifany, to preserve the integrity of the airway 100. The lesion 219 can beleft in the body to avoid potential complications from removing airwaytissue. The healthy airway wall 103 prevents gas escape across theairway wall 103. The smooth muscle and interior lining of the airway 100can remain substantially undamaged to allow mucociliary transport andother bodily functions that are important to overall health. Thisreduces the recovery time and avoids or mitigates problems associatedwith surgical techniques of removing or cutting through the airway wall.In contrast to lung resection procedures in which entire airways aresevered and removed, an intact denervated airway 100 can also ensurethat distal regions of the lung continue to function.

Large lesions can extend through the airway wall and can be formed todestroy unwanted tissue (e.g., cancerous tissues) positioned along theinner surface. Differential cooling can be used to form lesions burieddeep within the sidewall 103, spaced apart from the interior andexterior surfaces of the airway 100, or any other suitable location.U.S. patent application Ser. No. 12/463,304, filed on May 8, 2009, andU.S. patent application Ser. No. 12/913,702, filed on Oct. 27, 2010discloses various catheters and differential cooling techniques. Theinstrument 204 can cool tissues to keep the nontargeted tissue below atemperature at which cell death occurs. In some embodiments, the distalsection 214 has a cooling member (e.g., a cooling balloon) that absorbsthermal energy to keep nontargeted regions of the airway wall 103 at orbelow a desired temperature. The shape and size of lesions can also beadjusted as desired.

Natural body functions can help prevent, reduce, or limit tissue damage.If the bronchial artery branch 130 is heated, blood within the bloodvessels 130 can absorb the thermal energy and can then carry the thermalenergy away from the heated section of the branches 130. The lesion 219can surround a region of the blood vessel 130 without destroying thevessel 130. After the treatment is performed, the bronchial arterybranches 130 can continue to maintain the health of lung tissue.

The lesion depth D of FIG. 4 can be kept at or below a desired depth bycontrolling the amount of delivered energy. To avoid reaching smoothmuscle 114, the depth D can be equal to or less than about 3 mm, 2 mm,or 1 mm. For thick airway walls, the lesion depth D can be equal to orless than about 3 mm. For medium size airway walls, the lesion depth Dcan be equal to or less than about 2 mm. In young children with thinairway walls, the lesion depth D can be equal to or less than about 1mm. The lateral dimensions (e.g., width, length, etc.) of the lesion 219can be adjusted to ensure that targeted tissue is ablated.

FIG. 5 shows a system that includes a pair of separately deliverableinstruments 310, 312. The instrument 312 can be generally similar to theinstrument 204 of FIGS. 2-4, unless indicated otherwise. The instrument310 can be an intraluminal catheter deliverable through a lumen 101defined by an inner surface 102 of the airway 100. The illustrated innersurface 102 is defined by a folded layer of epithelium 110 surrounded bystroma 112 a. A layer of smooth muscle tissue 114 surrounds the stroma112 a. A layer of stroma 112 b is between the muscle tissue 114 andconnective tissue 124. Mucous glands 116, cartilage plates 118, bloodvessels 120, and nerve fibers 122 are within the stroma layer 112 b.Bronchial artery branches 130 and nerve trunks 45 are exterior to a wall103 of the airway 100. The illustrated arteries 130 and nerve trunks 45are within the connective tissue 124 surrounding the airway wall 103 andcan be oriented generally parallel to the airway 100. In FIG. 1, forexample, the nerve trunks 45 originate from the vagus nerves 41, 42 andextend along the airway 100 towards the air sacs. The nerve fibers 122are in the airway wall 103 and extend from the nerve trunks 45 to themuscle tissue 114. Nervous system signals are transmitted from the nervetrunks 45 to the muscle 114 via the nerve fibers 122.

The instrument 310 can be delivered along the trachea, esophagus, orother body structure in the vicinity of the treatment site. For example,the instrument 310 can extend through one or more organs to position anenergy emitter 314 proximate to the targeted tissue. Instruments 310,312 can cooperate to treat the targeted tissue therebetween. Theinstrument 310 can cool interior regions of the airway wall 103 to causethe formation of the lesion 219 at the outer periphery of the airwaywall 103. For radiofrequency ablation, the RF energy can travel betweenbipolar electrodes 314, 316. Tissue impedance causes heating that canreach sufficiently high temperatures to cause cell death. To protectnon-targeted tissues (e.g., interior tissue), the instrument 310 cancool the airway to keep the nontargeted tissue below a temperature atwhich cell death occurs.

Thermal energy can be absorbed by the instrument 312 to keep theexterior regions of the airway wall 103 at or below a desiredtemperature. Both instruments 310, 312 can provide cooling to formlesions generally midway through the airway wall 103. The amount ofenergy delivered and cooling capacity provided by the instruments 310,312 can be adjusted to shape and form lesions at different locations.

At least one of the instruments 310, 312 can be adapted to tunnelthrough tissue or between adjacent structures to allow it to reach thedesired location, for example, along the bronchi. Additionally oralternatively, the instruments 310, 312 may be adapted to adhere to orslide smoothly along tissue or to be urged against a structure (e.g.,trachea, esophagus, and/or bronchi) as the instrument is advanced.

FIG. 6 shows an instrument distal section 325 that includes atissue-receiving region 324 and an energy emitter 326. Thetissue-receiving region 324 has a concave surface 327 that generallymatches a convex surface of an airway. A radius of curvature of theportion 324 can be approximately equal to the radius of curvature of theairway. When the distal section 325 is held against an airway, theenergy emitter 326 can face targeted tissue.

FIG. 6A shows an instrument distal section 334 that includes an energyemitter 335 facing an airway 337. A distal tip 339 is shaped to keep theenergy emitter 335 facing the airway 337 as the distal section 334 ismoved distally, as indicated by an arrow 341. For example, the sloperegion 343 can help separate tissue 347 to facilitate distal movement ofthe distal section 334.

Referring to FIG. 7, an instrument distal section 330 includes atissue-receiving surface 327 and an opposing guiding surface 329. Theguiding surface 329 can slide smoothly along non-targeted tissue tofacilitate advancement of the distal section 330. The curvature,contour, or slope of the guiding surface 329 can be selected to urge thetissue-receiving surface 327 against an anatomical structure. An energyemitter 342 (illustrated as a plurality of electrodes) can direct energytowards tissue received by the tissue-receiving surface 327. To positionat least a portion of a nerve trunk in the surface 327, the tip 333 canbe inserted between an airway and adjacent tissue.

A wide range of different types of guides can partially or completelysurround a structure, such as the esophagus, trachea, or bronchus.Guides may include, without limitation, a plurality of arms (e.g., apair of arms, a set of curved or straight arms, or the like), a ring(e.g., a split ring or a continuous ring), or the like. FIGS. 8, 8A, and8B show embodiments of an instrument distal section 350 with a guide 352capable of surrounding a generally tubular structure. An emitter 354 ispositioned to deliver energy to a structure held by the guide 352. Thedistal section 350 can be moved along the airway using the guide 352.The guide 352 can be pulled off the airway and used to slide the distalsection 350 along another airway or other anatomical structure.

The illustrated guide 352 is a split ring lying in an imaginary planethat is generally perpendicular to a longitudinal axis 361 of the distalsection 350. To treat the main bronchus, resilient arms 353 a, 353 b canbe moved away from each other to receive the bronchus. The arms 353 a,353 b can snuggly hold the bronchus to allow atraumatic sliding. Surface355 a, 355 b can slide smoothly along an airway or other body structure.In some embodiments, the guide 352 is pivotally coupled to theinstrument shaft to allow the guide 352 to rotate as it moves along astructure.

FIG. 9 shows an instrument distal section 360 with guides in the form ofopenings 363. The openings 363 are circumferentially spaced about theperiphery of a main body 365. A vacuum can be drawn through one or moreof the openings 363 to hold the distal section 360 against tissue. Inother embodiments, fluids can be delivered out of one or more of theopenings 363 to push the distal section 360 in a desired direction.

FIG. 10 shows an instrument 400 with a distal section 412 wrapped arounda left main bronchus. The distal section 412 can be configured to assumea helical shape or spiral shape. As shown in FIG. 11, energy emitters414 a-414 n (collectively “414”) can deliver energy directly to theairway 100. An outer region 418 of the distal section 412 may not outputenergy to protect adjacent tissue. As such, the distal section 412 caneffectively emit energy towards the airway 100. In other embodiments,the distal section 412 can output energy in all directions. A protectivesleeve can be positioned over the applied distal section 412 to protectadjacent tissue. The sleeve can be made of an insulating material.

To treat the nerves 45, the electrodes 414 c, 414 j, 414 k can beactivated. The other electrodes 414 can remain inactive. In otherembodiments, a continuous electrode can extend along the length of thedistal section 414. The continuous electrode can be used to form ahelical or spiral shaped lesion. In certain embodiments, the continuouselectrode can have addressable sections to allow for selective ablation.

Airway cartilage rings or cartilage layers typically have asignificantly larger electrical resistance than airway soft tissue(e.g., smooth muscle or connective tissue). Airway cartilage can impedethe energy flow (e.g., electrical radiofrequency current flow) and makesthe formation of therapeutic lesions to affect airway trunks challengingwhen the electrode is next to cartilage. The electrodes 414 can bepositioned to avoid energy flow through cartilage. For example, theelectrode 414 can be positioned between cartilage rings. Most orsubstantially all of the outputted energy can be delivered between therings in some procedures. Tissue impedance can be measured to determinewhether a particular electrode is positioned next to a cartilage ring,in an intercartilaginous space, or at another location.

Referring again to FIG. 10, the instrument 400 may have a lumen toreceive a stylet to straighten and stiffen the preshaped distal section412 during introduction. After insertion, the stylet can be withdrawn toallow the preshaped distal section 412 to assume a treatmentconfiguration (e.g., a spiral configuration, a helical configuration, orthe like). Alternatively, the distal section 412 may be relativelyflexible and straight during introduction. A stylet having a shapecorresponding to a desired shape may be inserted into the instrument 400to impart the desired shape to the distal section 412. In a furtherembodiment, the instrument 400 may be shapeable or steerable using anactuator at its proximal end to allow it to be steered so as to surroundthe target tubular structure. Various steering mechanisms can be used,including, for example, one or more pull wires anchored to a distal tipat a point offset from the center line. The wire(s) can extend slidablythrough one or more lumens in the instrument 400 to the proximal endwhere they may be tensioned by an actuator so as to deflect the distalsection 412.

FIG. 12 shows a system for non-invasively denervating a bronchial tree.An external energy source 500 is connected to an energy delivery system510. The external energy source 500 can emit a beam of radiation totargeted tissue, such as nerve tissue. The beam of radiation can destroythe targeted tissue. The system can include, or be in the form of, aCyberKnife® Robotic Radiosurgery System from Accuray®, a TomoTherapy®radiation therapy system, or similar type of systems capable oftargeting moving tissue, thereby mitigating or limiting damage tonon-targeted tissue.

Beam radiation may be delivered from different remote locations todamage deep nerve tissue without damaging intervening tissues. Thesource of beam radiation may be a beam emitter 500 of an external beamradiotherapy system or a stereotactic radiation system 510. Because thelungs and bronchi move as the subject breathes, the system can beadapted to target moving tissues. By positioning the radiation beamemitter 500 at various locations relative to the patient's body 522,such systems may be used to deliver a radiation beam from various anglesto the targeted nerve tissue. The dose of radiation given to interveningtissues may be insufficient to cause injury, but the total dose given tothe target nerve tissue is high enough to damage (e.g., ablate) thetargeted tissue.

Ultrasound can be used to damage targeted tissue. High intensity focusedultrasound may be used to target and damage the nerve tissue. Theexternal energy source 500 can be a HIFU emission device. Alternatively,a catheter, an intra-luminal instrument, or other type of instrument forinsertion into the body can include a HIFU emission device. By way ofexample, the element 209 of FIG. 3 can be a HIFU emission device. Suchembodiments are well suited for delivery through another body structure,such as the esophagus or airway, to treat target tissue of an airway.The HIFU instrument may include ultrasound imaging capability to locatethe targeted tissues. The HIFU instrument can emit a plurality ofultrasound “beams” from different angles toward the target tissues. Theintensity of any one of the beams can be insufficient to damageintervening tissues. The beams can interfere at the target site andtogether have sufficient magnitude to damage the target nerve tissue.

The HIFU-based systems can be adapted to target moving tissues. Forexample, such systems may have a computer-controlled positioning systemwhich receives input from an ultrasound or other imaging system andcommands a positioning system in real time to maintain the HIFU devicein a fixed position relative to the target structure.

Instruments disclosed herein may be entirely or partially controlledrobotically or by a computer. Instruments may be attachable to acomputer-controlled robotic manipulator which moves and steers theinstruments. Robotic systems, such as the da Vinci® Surgical System fromIntuitive Surgical or the Sensei Robotic Catheter system from HansenMedical, Inc., or similar types of robotic systems, can be used. Theinstruments can have a proximal connector (e.g., an adaptor mechanism)that connects with a complementary fitting on the robotic system andlinks movable mechanisms of the instrument with control mechanisms inthe robotic system. The instrument connector can also provide electricalcouplings for wires leading to energy emitters, electrodes, microwaveantennae, or other electrically powered devices. The instrument mayfurther include sensor devices (e.g., temperature sensors, tissueimpedance sensors, etc.) which are also coupled via the connector of therobotic system. The robotic system can include a control module thatallows the physician to move and activate the denervation instrumentwhile visualizing the location of the instrument within the chest, forexample, using thoracoscopy, fluoroscopy, ultrasound, or other suitablevisualization technology. The instrument may also be computercontrolled, with or without robotic manipulation. A computer may receivefeedback (e.g., sensory data) from sensors carried by the instrument orelsewhere to control positioning, power delivery, or other parameters ofinterest. For example, in energy-based denervation embodiments, acomputer may be used to receive temperature data from temperaturesensors of the instrument and to control power delivery to avoidoverheating of tissue.

The instruments can access sites through blood vessels, as well asexternal to the organs. Robot surgery (including robotic cathetersystems), natural orifice access methods, and minimally invasive accessmethods such as using trocar access methods and thoracoscopy haveprovided clinicians with access procedure locations within the humanbody and also minimized patient morbidity and complications due tosurgery.

The assemblies, methods, and systems described herein can be used toaffect tissue which is located on the outside of hollow organs, such asthe lung, esophagus, nasal cavity, sinus, colon, vascular vessels andthe like or other solid organs. Various types of activatable elements(e.g., energy emitters) can be utilized to output the energy. Theactivatable elements can be sufficiently small to facilitatepercutaneous delivery to minimize or limit trauma to the patient.

The embodiments disclosed herein can treat the digestive system, nervoussystem, vascular system, or other systems. The treatment systems and itscomponents disclosed herein can be used as an adjunct during anothermedical procedure, such as minimally invasive procedures, openprocedures, semi-open procedures, or other surgical procedures (e.g.,lung volume reduction surgery) that provide access to a desired targetsite. Various surgical procedures on the chest may provide access tolung tissue, the bronchial tree, or the like. Access techniques andprocedures used to provide access to a target region can be performed bya surgeon and/or a robotic system. Those skilled in the art recognizethat there are many different ways that a target region can be accessed.The various embodiments h such claims are entitled. Accordingly, theclaims are not limited by the disclosure. described above can becombined to provide further embodiments. All of the U.S. patents, U.S.patent application publications, U.S. patent applications, foreignpatents, foreign patent applications and non-patent publicationsreferred to in this specification and/or listed in the Application DataSheet are incorporated herein by reference, in their entirety. Aspectsof the embodiments can be modified, if necessary to employ concepts ofthe various patents, applications and publications to provide yetfurther embodiments.

These and other changes can be made to the embodiments in light of theabove-detailed description. In general, in the following claims, theterms used should not be construed to limit the claims to the specificembodiments disclosed in the specification and the claims, but should beconstrued to include all possible embodiments along with the full scopeof equivalents to which such claims are entitled. Accordingly, theclaims are not limited by the disclosure.

What is claimed is:
 1. A method, comprising: providing an instrument toa user, the instrument including an energy emitter positioned at adistal section of the instrument; and providing instructions to theuser, the instructions comprising: moving the energy emitter through theskin of a subject; wrapping the distal section of the instrument aroundan airway of the bronchial tree of the subject to position the energyemitter with respect to nerve tissue along the airway of the bronchialtree; energizing the energy emitter to damage the nerve tissue usingenergy from the energy emitter while the energy emitter is positionedoutside of the airway; and removing the instrument from the subject. 2.The method of claim 1, wherein providing an instrument to a usercomprises causing the instrument to be manufactured and made availableto the user, and wherein providing instructions to the user comprisesproviding instructions for use or directions for accessing instructionsfor use, said instructions for use or directions being recorded on atangible medium.
 3. The method of claim 1, wherein the instructionsfurther comprise monitoring the airway so as to leave the airway intactthroughout the denervation process.
 4. The method of claim 1, whereinthe instructions for energizing the energy emitter to damage the nervetissue further comprise instructions for ablating a section of a nervetrunk to impede transmission of nervous system signals traveling alongthe airway.
 5. The method of claim 1, wherein the instructions forenergizing the energy emitter to damage the nerve tissue furthercomprise delivering at least one of radiofrequency energy, microwaveenergy, radiation energy, high intensity focused ultrasound energy, andthermal energy from the energy emitter to damage the nerve tissue. 6.The method of claim 1, wherein the instructions further comprisepercutaneously delivering the energy emitter proximate to the nervetissue prior to damaging the nerve tissue.
 7. The method of claim 1,wherein the instructions further comprise: moving an intraluminalinstrument through the subject's trachea and the airway; and deliveringenergy between the energy emitter of the instrument outside the airwayand the intraluminal instrument positioned within the airway to ablatethe nerve tissue.
 8. The method of claim 1, wherein the instructions forenergizing the energy emitter to damage the nerve tissue furthercomprise instructions for irreversibly damaging nerve tissue between thesubject's trachea and the subject's lung to at least partially block atransmission of nervous system signals and to cause a permanent decreasein smooth muscle tone of the portion of a bronchial tree.
 9. The methodof claim 1, wherein the instructions for energizing the energy emitterto damage the nerve tissue the nerve tissue further compriseinstructions for ablating the nerve tissue while monitoring the airwayso as not to pass the instrument through a wall of the airway.
 10. Themethod of claim 1, wherein the instructions for energizing the energyemitter to damage the nerve tissue further comprise instructions fordestroying the nerve tissue while monitoring the airway so as not tosubstantially damage blood vessels of the airway.
 11. The method ofclaim 1, wherein the instructions for energizing the energy emitter todamage nerve tissue further comprise instructions for damaging nervetissue positioned along a main bronchus of the bronchial tree.
 12. Themethod of claim 1, wherein the instructions further comprise visualizingthe outside of the airway while positioning the energy emitter using avisualization device selected from a group consisting of a thoracoscope,an ultrasonic device, and a fluoroscopy system.
 13. The method of claim1, wherein the instructions for moving the energy emitter through theskin of a subject further comprise moving the energy emitter through aport, a cannula, or a sleeve extending through the skin of the subject.14. A method, comprising: providing an instrument to a user; andproviding instructions to the user, the instructions comprising:percutaneously delivering a distal section of the instrument through theskin of a subject and wrapping the distal section of the instrumentaround an airway of a bronchial tree of the subject such that the distalsection is positioned to damage nerve tissue of the bronchial tree; anddelivering energy to a first portion of the bronchial tree using theinstrument to substantially inhibit nervous system signals fromtraveling to a second portion of the bronchial tree.
 15. The method ofclaim 14, wherein providing an instrument to a user comprises causingthe instrument to be manufactured and made available to the user, andwherein providing instructions to the user comprises providinginstructions for use or directions for accessing instructions for use,said instructions for use or directions being recorded on a tangiblemedium.
 16. The method of claim 14, wherein the instructions furthercomprise damaging a nerve trunk positioned along a main bronchus. 17.The method of claim 14, wherein the instructions for denervating a firstportion of the bronchial tree further comprise instructions for damagingnerve tissue positioned between the subject's trachea and lung.
 18. Themethod of claim 14, wherein the instructions for denervating a firstportion of the bronchial tree further comprise instructions for ablatinga sufficient amount of nerve tissue to prevent nervous system signalsfrom traveling to substantially all bronchial branches of the bronchialtree.
 19. The method of claim 14, wherein the instructions fordenervating a first portion of the bronchial tree further compriseinstructions for removing the instrument without destroying the airway.20. The method of claim 14, wherein the instructions for percutaneouslydelivering a distal section of the instrument through the skin of asubject further comprise instructions for delivering a distal section ofthe instrument through a port, a cannula, or a sleeve extending throughthe subject's skin.